Plasma kallikrein (pKal) is the primary bradykinin-generating enzyme in the circulation and a component of the plasma kallikrein-kinin system (KKS). Colman, R. W., and Schmaier, A. H. (1997) Blood 90, 3819-3843. The activation of pKal occurs via the contact system which has been demonstrated to be causative in the disease pathology associated with hereditary angioedema (HAE). Zuraw, B. L., and Christiansen, S. C. (2008) Expert Opin Investig Drugs 17, 697-706. Bradykinin is a key mediator of pain, inflammation, edema and angiogenesis. Maurer, M., et al. (2011) Allergy 66, 1397-1406; Colman, R. W. (2006) Curr Pharm Des 12, 2599-2607.